The objective of this proposed study is to ascertain the alleged ethnic differences in the circulatory, metabolic and psychological effects of ethanol as well as in the rate of metabolism of ethanol between American Indians and Caucasians. Furthermore, we intend to elucidate the underlying biochemical and pharmacogenetic mechanisms responsible for this difference. For this purpose, firstly, we plan to determine the kinetics of plasma ethanol and acetaldehyde disappearance by gas chromatography, and to measure (a) the circulatory parameters, respiration rate, skin temperature, (b) various psychological performances and (c) plasma glucose, lactate, pyruvate, urate and lipids levels as well as the plasma catecholamine, kallikrein and bradykininogen levels before and during ethanol administration. Secondly, it is planned to study the specific activity of human liver ADH, MEOS and catalase obtained from American Indians and to compare these with those from Caucasians. Furthermore, the liver and placenta ADH isoenzymes in both ethnic groups will be characterized by starch gel electrophoresis. In these studies, we shall attempt to define pharmacogenetic patterns which correlate the biochemical observations with various pharmacological responses to ethanol and with ethanol tolerance in American Indians.